Multi-biomarker approach demonstrates flavanol cardio benefits: Study

An eight-week study of monomeric and oligomeric flavanols (MOPs) employing a “multi-biomarker approach” in a healthy population of smokers has shown cardiovascular benefits.

Mindful of the European Food Safety Authority’s (EFSA) tough stance on antioxidant science, the Maastricht University researchers tested a number of biomarkers and found a significant increase in cardiovascular-related measures when the results were combined.

The most significant change occurred in the ratio of glutathione to glutathione disulphide in erythrocytes. It was 22% higher in the supplemented subjects.

They also found OPCs reduced bacterial endotoxins and expression of inflammatory genes in leukocytes and reduced serum total cholesterol and LDL cholesterol.

“However, integrating all measured effects into a global vascular health index and taking into account that the trial was performed with healthy subjects,”​ the researchers, led by Dr. Antje Weseler concluded.

“a representative panel of markers”​​

They commented on some of the challenges the European Union nutrition and health claims regulation (NHCR) has presented to the field of nutrition science, especially in regard to biomarkers.

“Food scientists are facing the challenge to prove the clinical efficacy of nutrients that modulate human physiology in a subtle and non-specific manner,”​ the observed.

“In drug research, where the one-target-one-hit concept is imperative, randomized clinical trials with a well-defined single endpoint are the gold standard of efficacy testing. However, a single endpoint neither sufficiently reflects the multifarious nature of nutrients’ functions in humans nor the complexity of pathomechanisms underlying virtually all diseases.”​

“Our study pioneered the implementation of a pragmatic solution for this problem: Carefully select a representative panel of markers that reflect the major relevant pathological aberrations and integrate all measured effects into a global health index.”​

Method​

The researchers recruited smokers because they sought a healthy but slightly distressed group to test against the placebo group.

The double-blind, randomised, placebo-controlled intervention study was comprised of 28 middle-aged, smoking Dutch males to take either placebo or 200 mg per day of MOFs from grape seeds.

“​The meticulous selection of outcome parameters led to a spectrum of makers that comprised established as well as novel cardiovascular risk factors and systemic biomarkers reflecting the most essential pathomechanisms in the human vasculature on a functional and (sub)cellular level,”​ the researchers wrote.

“The integration of the changes in these biomarkers into a vascular health index enabled us to demonstrate the beneficial effects of MOF on vascular health in general. This is the first trial that applies an integrative biomarker approach in order to determine the health effects of a dietary supplementation in the human vasculature.”​

The study was partially sponsored by the International Nutrition Company along with a Seventh Framework Programme European Union grant under the Flaviola project.

1 comment

Talking Up Low Scientific Rigor?

Posted by Leto Atreides,
24 January 2012 - 06:57 GMT

Neither the summary by Shane Starling nor the authors’ interpretation of their work is meaningful in the context of assessing the potential impact of a dietary intervention on cardiovascular health, nor is it justified by the data provided in this publication. Besides the point that their study design exhibits significant gaps at various level, the authors conclude that they could not demonstrate significant effects following an 8-week MOF supplementation as compared to placebo when measuring: “…macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity…”. In other words, there was no effect! To pick and choose outcome measures and to subject them to a ‘novel’ integrated statistical analysis in order to imply meaningful outcomes is neither novel nor innovative, nor is there any support for the assumption that this specific approach is in any way causally related to cardiovascular morbidity, mortality or population-based health. While some of the biomarkers chosen by this team of investigators do represent accepted endpoints of primary or secondary prevention in the context of cardiovascular disease, none of these changed as a function of MOF supplementation! Consequently, many of the conclusions, interpretations, and communication elements derived from this work are unsubstantiated, and grossly misleading! [How misleading can be seen in the summary by Shane Starling!] Moreover, if the authors had an ‘a priori’ conviction that their ‘novel’ way of assessing the impact of dietary components on cardiovascular health represents a relevant and meaningful advancement on current methods, why did they not choose this assessment as the primary outcome measure in the registration of their clinical trial instead of FMD? In my mind the answer is obvious, as I believe this idea was a posteriori-child of the efforts by the authors to interpret a nil outcome of their study in ways that would increase the chance of publishing this work! However, applying clinical study principles as required by many scientific journals in the context of CONSORT (Consolidated Standards Of Reporting Trials), their intervention had no effect over placebo when judged by the registered primary outcome measure (FMD). To be completely clear, I agree with the authors that all available data should be assessed and evaluated, but this needs to happen in accordance with rigorous scientific principles, as it is all too easy to find what one was looking for. In this context, I would also like to express my great astonishment with regard to the peer-review process as organized and executed via the handling editor and the reviewers.